This Week in Radiation Science

Every few weeks, we highlight a recent research article we think will be of significant interest to the radiation science community. Not all of the research articles will be from our members or even from MD Anderson, but instead from the broader Radiation Oncology community. We welcome suggestions at CRORadmin@mdanderson.org.

This week, we are highlighting a paper from Skinner’s group titled “Proteomic Profiling Identifies PTK2/FAK as a Driver of Radioresistance in HPV-negative Head and Neck Cancer.” Through proteomic and transcriptomic analysis, the group identifies focal adhesion kinase (or FAK) as overexpressed in patients with radioresistant tumors. While other famous proteins were identified as well (FGFR, EGFR, and ERK1), chemical inhibition of FAK but not FGFR was associated with sensitization of head and neck squamous carcinoma cell lines to radiation. Even more importantly, patients whose tumors had increased copy numbers of the FAK gene (i.e. PTK2 gene), did significantly worse when evaluated for disease free survival. Similar finding was revealed in an independent patient cohort.

This work nicely complements an earlier report on the importance of -integrin and EGFR in head and neck cancer cell response to radiation therapy (Eke et al, 2015. “Simultaneous β1-integrin-EGFR targeting and radiosensitization of human head and neck cancer”). Targeting both pathways allowed the investigators to overcome radiation resistance suggesting that β1-integrin and EGFR played critical roles in cell response after radiation damage. While targeting EGFR through cetuximab has already been employed in the clinic, β1-integrin targeting has not been explored in head and neck cancer therapy. β1-integrin signaling is mediated through FAK, suggesting that FAK may be equally important in this phenomenon.

The mechanism by which FAK influences cell response and resistance to radiation remains to be explored. Eke et al suggested that the ability of cells to control their physical shape through β1-integrin-FAK signaling axis may influence their ability to initiate cell death following damage. On the other hand, Skinner et all suggest that the cell’s ability to respond to and repair DNA damage may be responsible for their finding, revealing a possibility of an undiscovered link between focal adhesions and DNA damage response and repair. Given that radiation is one of the most effective treatments for head and neck cancer, further understanding of this mechanism and its clinical utility will be critical for our ability to make cancer history.